Perioperative discontinuation of SGLT2-inhibitors and cardiac complications after noncardiac surgery: secondary analysis of two prospective observational cohort studies

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BACKGROUND: International clinical practice guidelines recommend discontinuing sodium-glucose cotransporter-2 inhibitors (SGLT2i) 3-4 days before surgery to prevent euglycemic diabetic ketoacidosis, chiefly on the basis of case reports/series. Whether SGLT2i discontinuation may increase the risk of postoperative cardiovascular complications is unclear. METHODS: In a secondary analysis of the Basel-PMI (NCT02573532) and PMI-Vital (NCT05866874) prospective cohort studies in major noncardiac surgery, the exposure of interest was continuing, or stopping, SGLT2i in participants receiving chronic SGLT2i therapy. The primary outcome was an ordinal composite of acute heart failure hospitalisation and cardiovascular death within 90 days of surgery, adjusting for prespecified covariates. Secondary outcomes included the incidence of euglycemic diabetic ketoacidosis within 7 days. RESULTS: Among 451 study participants receiving SGLT2i (mean age 72 (range: 47-86) yr; 22% women), 404/451 (89.6%) had diabetes mellitus, and 166/451 (36.9%) had chronic heart failure. SGLT2i were discontinued before surgery in 393/451 (87.1%) participants (39.2% for 1 day, 34.4% for 2 days, 13.5% for ≥3 days). Cardiovascular complications occurred in 1/58 (1.7%) participants who continued SGLT2i, compared with 10/177 (5.7%) stopping for 1 day, 13/155 (8.4%) stopping for 2 days and 7/61 (11.5%) stopping for ≥3 days (P=0.011; adjusted odds ratio: 1.58 [95% confidence interval: 1.08-2.30] per discontinued day). Euglycemic diabetic ketoacidosis occurred in 1/451 participants after SGLT2i discontinuation. CONCLUSIONS: Perioperative SGLT2i discontinuation was associated with a substantially increased risk of 90-day cardiac complications. This suggests potential harm in current guideline recommendations; randomised controlled trials are needed to confirm these findings. STUDY REGISTRATION: NCT02573532, NCT05866874.

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